Rheumatoid ArthritisPhase 1/2NCT02328027
99mTc-rhAnnexin V-128 a Phase I/IIa Study in Patients With Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS)
A Phase 1/2 study testing 99mTc-rhAnnexin V-128 in people with Rheumatoid Arthritis and Ankylosing Spondylitis, run by Advanced Accelerator Applications at 1 site in Switzerland.
Trial summary
This was a monocentric, open label, Phase I-IIa study. Eligible patients who signed the ICF received two single intravenous (IV) bolus of the imaging agent 99mTc-rhAnnexin V-128. The first dose was administered on Day 1, and the second dose on Day 42 (±2 weeks). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis, Ankylosing Spondylitis
- What is being tested?
- 99mTc-rhAnnexin V-128
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteSwitzerland
- Study dates
- 11 Dec 2014to 17 Oct 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients diagnosed with RA based on ACR/EULAR 2010 criteria (score >=6), or Patients diagnosed with AS based on the ASAS criteria. Patients with RA must have serology assessment performed and documented at the time of enrollment.
- Patient with RA active disease (DAS > 2,6) and the introduction of a Bi-DMARD should be indicated. RA patients must have been treated with DMARD (methotrexate, leflunomide and sulfasalazine) or combination of these treatments for at least 3 months. Treatment will be pursued while on study.
- or RA patients must have been previously treated with Bi-DMARD before initiation of the new Bi-DMARD treatment. The non-response of the previous Bi-DMARD treatment must be documented.
- or Patients with AS with insufficiently controlled disease while under NSAID and indication for Bi-DMARD. These patients must be under NSAID for at least 3 months and under the same NSAID for at least 1 month prior to enrollment.
- ≥ 18 years old
- Karnofsky ≥ 80%
Show all 10Show fewer
- Negative Pregnancy test for women with childbearing potential
- For women with childbearing potential, use of two reliable means of contraception (e.g., hormonal contraceptive, patch, vaginal ring, intrauterine device, associated with other barrier method of contraception such as the use of condoms) , throughout their participation in the study
- Absence of ECG anomaly
- written ICF signed
Who cannot join
- Pregnancy or lactation
- Liver impairment (ALT, AST or Bilirubin > 2 ULN) at screening visit or baseline
- Kidney impairment (serum creatinine > 1.5 mg/dL)
- History of congestive heart failure (NYHA III \& IV)
- History of malignant disease within 5 years
- History of any disease or relevant physical or psychiatric condition or abnormal physical finding which may interfere with the study objectives at the investigator judgment
- Known hypersensitivity to the investigational drug or any of its components
- Participation to another clinical trial within 4 weeks before study inclusion except for patients who have participated or who are currently participating in an interventional study without any study drug administration.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Centre Hospitalier Universitaire Vaudois
Lausanne, Canton of Vaud, 1011
About this study
Official title: A Phase I-IIa Study of Safety, Tolerance, Pharmacokinetics, Dosimetry and Benefice of Early Nuclear Medicine Imaging of 99mTc-rhAnnexin V-128 in Patients With Rheumatoid Arthritis or Ankylosing Spondylitis
This was a monocentric, open label, Phase I-IIa study. Eligible patients who signed the ICF received two single intravenous (IV) bolus of the imaging agent 99mTc-rhAnnexin V-128. The first dose was administered on Day 1, and the second dose on Day 42 (±2 weeks).
All patients were to start a new disease modifying treatment for RA or AS on Day 2. This disease modifying treatment was at the discretion of the investigator and was not chosen by the sponsor.
Safety was monitored at every visit. Whole body scintigraphic imaging was performed at Day 1 and Day 42 after 99mTc-rhAnnexin V-128 dosing. Clinical disease assessments were performed at screening, Day 42 and Day 90 to assess response to RA or AS treatment. Blood was drawn to test for 99mTc-rhAnnexin V-128 immunogenicity at screening and on Days 30, 56 and 90. Patients participating in the pharmacokinetic (PK)/dosimetric sub-study had additional assessments in the 24 hours following the Day 1 dose of 99mTc-rhAnnexin V-128.
Read the detailed description
The study was terminated early after the inclusion of 16 of the 20 planned patients. The sponsor decided to terminate the study earlier than planned due to slow accrual. Novartis acquired Advanced Accelerator Applications SA.
- Conditions
- Rheumatoid Arthritis, Ankylosing Spondylitis
- Being tested
- 99mTc-rhAnnexin V-128
- Medical subject headings
- Arthritis, Rheumatoid, Spondylitis, Ankylosing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
99mTc-rhAnnexin V-128Drug
1 single intravenous bolus administration of 250 MBq, at Day 1 and at Day 42.
| Study group | Role | What they receive |
|---|---|---|
| 99mTc-rhAnnexin V-128, i.v. | Experimental | Patients will receive 2 administrations of the 99mTc-rhAnnexin V-128 medical imaging agent: one at Day 1 and the other at Day 42. Receives: Drug: 99mTc-rhAnnexin V-128 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death
An adverse event (AE) is defined as any untoward medical occurrence in a patient and which does not necessarily have a causal relationship with the study medication. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease, temporally associated with the use of a study medication, whether or not causally related to the study medication. TEAEs are defined as all AEs reported after the first dose. An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, life-threatening, results in persistent or significant disability/incapacity, results in congenital anomaly or birth defect, requires in-patient hospitalization or leads to prolongation of hospitalization.
Measured: From screening up to Day 90
Secondary outcomes (9)
Area Under the Curve Extrapolated to Infinity (AUC) of 99mTc-rhAnnexin V-128
AUC is defined as area under the curve extrapolated to infinity of 99mTc-rhAnnexin V-128.
Measured: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours)
Distribution Volume (Vz) of 99mTc-rhAnnexin V-128
Vz is defined as the distribution volume of 99mTc-rhAnnexin V-128.
Measured: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours)
Systemic Clearance (Cl) of 99mTc-rhAnnexin V-128
Cl is defined as the systemic clearance of 99mTc-rhAnnexin V-128.
Measured: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours)
Elimination Half-life (t1/2) of 99mTc-rhAnnexin V-128
t1/2 is defined as the elimination half-life of 99mTc-rhAnnexin V-128.
Measured: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours)
Serum Concentration of rhAnnexin V-128 Based on Enzyme-linked Immunosorbent Assay (ELISA) Analysis
Serum concentration of rhAnnexin V-128 based on ELISA analysis were to be evaluated and reported overtime.
Measured: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00 and 24.00 hours)
99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)
Total radioactivity count per minute in whole blood samples were reported.
Measured: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50 to 2.00, 3.00 to 4.00 and 24.00 hours)
99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)
Total radioactivity count per minute in serum samples were reported.
Measured: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50 to 2.00, 3.00 to 4.00, 6.00 and 24.00 hours)
99mTc-rhAnnexin V-128 Urine Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)
Total radioactivity count per minute in urine samples were reported.
Measured: Day 1 (0 (Predose), 1.00, 4.00, 6.00 and 24.00 hours)
Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis
Urine samples (10 mL aliquots) were analysed as a function of time by SEC-HPLC technique at the local laboratory in order to gain information on the chemical status of 99mTc-rhAnnexin V-128 and on the presence of 99mTc-rhAnnexin V-128-related species.
Measured: Day 1 (0 (Predose), up to 1.00 hour, from 1.00 to 4.00 hours, from 4.00 to 6.00 hours, from 16.00 to 24.00 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2014 (estimated)
- Study start11 Dec 2014
- Primary completion17 Oct 2017
- Study completion17 Oct 2017
Why it stopped: Low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advanced Accelerator Applications
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John Prior, MD, PhD, Principal investigator, CHUV LausanneNovartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02328027
- Sponsor's protocol ID
- 1002
- Other IDs
- CAAA113A22101
- Status last verified
- Sep 2020
- First submitted
- 18 Dec 2014
- Last updated
- 8 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-IIa Study of Safety, Tolerance, Pharmacokinetics, Dosimetry and Benefice of Early Nuclear Medicine Imaging of 99mTc-rhAnnexin V-128 in Patients With Rheumatoid Arthritis or Ankylosing Spondylitis
- ClinicalTrials.gov ID
- NCT02328027
- Acronym / sponsor ID
- 1002
- Conditions
- Rheumatoid Arthritis, Ankylosing Spondylitis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Advanced Accelerator ApplicationsIndustry (pharma, biotech, devices)
- Study start
- 11 Dec 2014 (actual)
- Primary completion
- 17 Oct 2017 (actual)
- Study completion
- 17 Oct 2017 (actual)
- First posted
- 31 Dec 2014 (estimated)
- Results
- Posted 9 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a monocentric, open label, Phase I-IIa study. Eligible patients who signed the ICF received two single intravenous (IV) bolus of the imaging agent 99mTc-rhAnnexin V-128. The first dose was administered on Day 1, and the second dose on Day 42 (±2 weeks).
All patients were to start a new disease modifying treatment for RA or AS on Day 2. This disease modifying treatment was at the discretion of the investigator and was not chosen by the sponsor.
Safety was monitored at every visit. Whole body scintigraphic imaging was performed at Day 1 and Day 42 after 99mTc-rhAnnexin V-128 dosing. Clinical disease assessments were performed at screening, Day 42 and Day 90 to assess response to RA or AS treatment. Blood was drawn to test for 99mTc-rhAnnexin V-128 immunogenicity at screening and on Days 30, 56 and 90. Patients participating in the pharmacokinetic (PK)/dosimetric sub-study had additional assessments in the 24 hours following the Day 1 dose of 99mTc-rhAnnexin V-128.
Detailed description
The study was terminated early after the inclusion of 16 of the 20 planned patients. The sponsor decided to terminate the study earlier than planned due to slow accrual. Novartis acquired Advanced Accelerator Applications SA.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 99mTc-rhAnnexin V-128, i.v. | Experimental | Drug: 99mTc-rhAnnexin V-128Patients will receive 2 administrations of the 99mTc-rhAnnexin V-128 medical imaging agent: one at Day 1 and the other at Day 42. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients diagnosed with RA based on ACR/EULAR 2010 criteria (score >=6), or Patients diagnosed with AS based on the ASAS criteria. Patients with RA must have serology assessment performed and documented at the time of enrollment.
- Patient with RA active disease (DAS > 2,6) and the introduction of a Bi-DMARD should be indicated. RA patients must have been treated with DMARD (methotrexate, leflunomide and sulfasalazine) or combination of these treatments for at least 3 months. Treatment will be pursued while on study.
- or RA patients must have been previously treated with Bi-DMARD before initiation of the new Bi-DMARD treatment. The non-response of the previous Bi-DMARD treatment must be documented.
- or Patients with AS with insufficiently controlled disease while under NSAID and indication for Bi-DMARD. These patients must be under NSAID for at least 3 months and under the same NSAID for at least 1 month prior to enrollment.
- ≥ 18 years old
Key exclusion criteria (8 listed)
- Pregnancy or lactation
- Liver impairment (ALT, AST or Bilirubin > 2 ULN) at screening visit or baseline
- Kidney impairment (serum creatinine > 1.5 mg/dL)
- History of congestive heart failure (NYHA III \& IV)
- History of malignant disease within 5 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 99mTc-rhAnnexin V-1281 single intravenous bolus administration of 250 MBq, at Day 1 and at Day 42. | Drug | 99mTc-rhAnnexin V-128, i.v. |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death
Time frame: From screening up to Day 90
An adverse event (AE) is defined as any untoward medical occurrence in a patient and which does not necessarily have a causal relationship with the study medication. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease, temporally associated with the use of a study medication, whether or not causally related to the study medication. TEAEs are defined as all AEs reported after the first dose. An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, life-threatening, results in persistent or significant disability/incapacity, results in congenital anomaly or birth defect, requires in-patient hospitalization or leads to prolongation of hospitalization.
9 secondary outcomes
Area Under the Curve Extrapolated to Infinity (AUC) of 99mTc-rhAnnexin V-128
Time frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours)
Distribution Volume (Vz) of 99mTc-rhAnnexin V-128
Time frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours)
Systemic Clearance (Cl) of 99mTc-rhAnnexin V-128
Time frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours)
Elimination Half-life (t1/2) of 99mTc-rhAnnexin V-128
Time frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours)
Serum Concentration of rhAnnexin V-128 Based on Enzyme-linked Immunosorbent Assay (ELISA) Analysis
Time frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00 and 24.00 hours)
99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)
Time frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50 to 2.00, 3.00 to 4.00 and 24.00 hours)
99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)
Time frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50 to 2.00, 3.00 to 4.00, 6.00 and 24.00 hours)
99mTc-rhAnnexin V-128 Urine Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)
Time frame: Day 1 (0 (Predose), 1.00, 4.00, 6.00 and 24.00 hours)
Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis
Time frame: Day 1 (0 (Predose), up to 1.00 hour, from 1.00 to 4.00 hours, from 4.00 to 6.00 hours, from 16.00 to 24.00 hours)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Prior, MD, PhD principal investigator
CHUV Lausanne
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 99mTc-rhAnnexin V-128 in people with Rheumatoid Arthritis and Ankylosing Spondylitis, run by Advanced Accelerator Applications at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death (time frame: From screening up to Day 90). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.